Expansion of Signal Transduction Pathways in Fungi by Extensive Genome Duplication

Plants and fungi use light and other signals to regulate development, growth, and metabolism. The fruiting bodies of the fungus Phycomyces blakesleeanus are single cells that react to environmental cues, including light, but the mechanisms are largely unknown [1]. The related fungus Mucor circinelloides is an opportunistic human pathogen that changes its mode of growth upon receipt of signals from the environment to facilitate pathogenesis [2]. Understanding how these organisms respond to environmental cues should provide insights into the mechanisms of sensory perception and signal transduction by a single eukaryotic cell, and their role in pathogenesis. We sequenced the genomes of P. blakesleeanus and M. circinelloides and show that they have been shaped by an extensive genome duplication or, most likely, a whole-genome duplication (WGD), which is rarely observed in fungi [3–6]. We show that the genome duplication has expanded gene families, including those involved in signal transduction, and that duplicated genes have specialized, as evidenced by differences in their regulation by light. The transcriptional response to light varies with the developmental stage and is still observed in a photoreceptor mutant of P. blakesleeanus. A phototropic mutant of P. blakesleeanus with a heterozygous mutation in the photoreceptor gene madA demonstrates that photosensor dosage is important for the magnitude of signal transduction. We conclude that the genome duplication provided the means to improve signal transduction for enhanced perception of environmental signals. Our results will help to understand the role of genome dynamics in the evolution of sensory perception in eukaryotes.Office of Science (USA) DE-AC02-05CH11231Ministerio de Economía y Competitividad BIO2005-25029-E , BIO2015-67148-RJunta de Andalucía P06-CVI-0165

Lecciones y practicum de Derecho Constitucional

El presente proyecto de innovación docente persigue un doble objetivo: la actualización de los contenidos de Lecciones de Derecho Constitucional II y la reorganización y difusión de las prácticas de Derecho Constitucional II. Mientras que la primera finalidad ya ha sido satisfecha, la segunda se está desarrollando al tiempo en el que se imparten las lecciones por parte de los distintos profesores.Departamento de Derecho Constitucional, Procesal y Eclesiástico del Estad

Three double-dose reinforced hepatitis B revaccination scheme for patients with cirrhosis unresponsive to the standard regimen: an open-label randomised clinical trial

© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.[Objective] We aimed to compare the response rates between two different hepatitis B virus vaccination schedules for cirrhotic subjects who were non-responders to the first three 40 µg doses (month 0-1-2), and identify factors associated with the final response.[Design] A total of 120 cirrhotic patients (72.5% decompensated) were randomised at a 1:1 ratio to receive a single 40 µg booster vaccination at month 6 (classical arm) versus an additional round of three new 40 µg doses administered at monthly intervals (experimental arm). The main outcome was the rate of postvaccinal anti-hepatitis B surface antibodies levels ≥10 mIU/mL.[Results] Efficacy by ITT analysis was higher in the experimental arm (46.7%) than in the classical one (25%); OR 2.63, p=0.013. The experimental arm increased response rates compared with the classical one from 31% to 68% (OR 4.72; p=0.007), from 24.4% to 50% (OR 3.09; p=0.012) and from 24.4% to 53.8% (OR 3.62; p=0.007), in Child A, Model for End-Stage Liver Disease (MELD) <15 and MELD-Na<15 patients, respectively. Patients with more advanced liver disease did not benefit from the reinforced scheme. Both regimens showed similar safety profiles. Multivariable analysis showed that the experimental treatment was independently response associated when adjusted across three logistic regression models indicating equivalent cirrhosis severity.[Conclusion] For cirrhotic patients, the revaccination of non-responders to the first three dose cycle, with three additional 40 µg doses, achieved significantly better response rates to those obtained with an isolated 40 µg booster dose.[Trial registration number] NCT01884415.This study project was awarded competitive public funding for Independent Research from the Spanish Government Ministry of Health and Social Politics in 2011 via the Carlos III Health Institute (EC11-452). Javier Ampuero is supported by grants from the Carlos III Health Institute (GLD19/00100 and PI19/01404). IBiS was created as a partnership between the Junta of Andalusia Department of Health, the Department of Innovation, Science and Business of the Junta of Andalusia, the Andalusian Health Service, the University of Seville and the Spanish National Research Council.Peer reviewe